Self-emulsifying and lyotropic nanocarriers enhance solubility and antiparasitic efficacy of artesunic acid against different strains of Schistosoma mansoni.

Schistosomiasis currently relies on the long-term use of a single drug, praziquantel (PZQ). Artesunic acid (AcART) has emerged as a promising alternative, as it is efficient against juvenile worms. However, like PZQ, it has low aqueous solubility. Self-Emulsifying Drug Delivery Systems (SEDDS) and Lyotropic Liquid Crystal Nanoparticles (NPs-LLC) present advantages for oral administration, including enhanced solubility and protection of the drug from first-pass metabolism. This study compared the in vitro and in vivo efficacy of AcART incorporated into SEDDS and NPs-LLC against juvenile and adult worms of two different Schistosoma mansoni strains. In vitro phenotypic assays with AcART incorporated into both SEDDS and NPs-LLC demonstrated a progressive decrease in parasite viability, significant tegumental changes, inhibition of oviposition, and 100 % mortality at a concentration 6.25 µg/mL. In vivo treatments performed at 21- and 60-days post-infection with AcART formulated in SEDDS and NPs-LLC led to a significant reduction in worms' burden and eggs eliminated in feces compared to the control group. The SEDDS nanosystems (drug-free) influenced the in vitro results, whereas the NPs-LLC (drug- free) did not influence any of the assays. Our findings demonstrate that these nanosystems enhance the efficacy of AcART against both BH and SE strains of S. mansoni, even at substantially lower concentrations than conventional formulations. This represents an innovative approach for the treatment of schistosomiasis, with potential applications to other neglected diseases.